EP0376041A2 — C63-Amide derivatives of 34-de(acetylglucosaminyl)-34-deoxy-teicoplanins

USPTO Abstract

The invention is directed to C⁶³-amide derivatives of 34-de(acetylglucosaminyl)-34-deoxy-teicolplanins of the formula I wherein: A represents N[(C₉-C₁₂)aliphatic acyl]-beta-D-2-deoxy-2-aminoglucopyranosyl: B is hydrogen or a protecting group of the amine function; M represents alpha-D-mannopyranosyl; Y represents a di- or poly-amine group of the formula -NR-[(CH₂) m NR¹] n -X-[(CH₂) k NR²] n -(CH₂) p -NR³R⁴ wherein: R is hydrogen or linear or branched (C₁-C₈)alkyl; R¹ is hydrogen or linear or branched (C₁-C₈)alkyl; R² is hydrogen or linear or branched (C₁-C₈)alkyl; R³ and R⁴ are each independently hydrogen, linear or branched (C₁-C₈)alkyl optionally bearing a NH₂, OH or SH substituent or taken together with the adjacent nitrogen atom, form a 5 to 7 membered saturated heterocyclic ring which may contain a further heteroatom selected from -S-, -O- and -NR⁵- wherein R⁵ is hydrogen, (C₁-C₄)alkyl, phenyl, or phenyl-(C₁-C₄)alkyl m , k and p each independently represent an integer from 2 to 8; n and h , each independently, represent an integer from 0 to 4; X represents a single bond, or when n is 1, taken together with the adjacent group NR¹, it may represent a bifunctional radical of the formula: wherein r and s each independently represent an integer from 1 to 6 with the proviso that their sum is an integer from 3 to 8; and their addition salts with acids. The derivatives are prepared by reacting 34-de(acetylglucosaminyl)-34-deoxy-teicoplanins with an active esters forming reagent such as chloroacetonitrile and then contacting said active esters with the appropriate di- or poly-amine. The amide derivatives are active against Gram-positive microorganisms, in particular against Group A Streptococci .